Taking advantage of the increased spectral resolution offered by the W-band ESR spectrometer, we have examined, at pH 7 and pH 12, ESR spectra of human RPE's of young, intermediate and old individuals. The data show remarkable changes in ESR signal of the human RPE with age. Interestingly, distinct changes in the magnetic parameters of the W-band ESR signal of RPE can be detected as early as in the second decade of the human life. Since purified melanosomes isolated from RPE's, exhibited ESR signals with spectral parameters identical to those of the corresponding RPE cells, we may conclude that the observed ESR signal is entirely due to these cells melanin. While we have not identified yet the molecular nature of the observed paramagnetic changes with aging, it is probable that they indicate significant modification of the melanin structure.